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Naveed Sattar

Publications and source records attributed to Naveed Sattar.

At least 19 recordsLinked to original sources
PubMed2026

Effect of semaglutide on kidney outcomes in the SELECT, FLOW, and SOUL trials: a prespecified pooled analysis.

BACKGROUND: The GLP-1 receptor agonist semaglutide reduces clinically important kidney outcomes in people with type 2 diabetes and chronic kidney disease (CKD). We aimed to assess the pooled effects of semaglutide on kidney outcomes in prespecified analyses of participant-level data from the diverse populations of the SELECT, FLOW, and SOUL randomised placebo-controlled trials. METHODS: Participants with CKD (FLOW) or atherosclerotic cardiovascular disease (SELECT and SOUL) were randomly assigned semaglutide (once-weekly subcutaneous 1&#xb7;0 mg [FLOW], once-weekly subcutaneous 2&#xb7;4 mg [SELECT], or once-daily oral 14 mg [SOUL]) or matching placebo, added to standard of care. The primary outcome in this pooled analysis was time to first occurrence of a kidney composite, defined as onset of persistent 50% or greater reduction in estimated glomerular filtration rate (eGFR), kidney failure (persistent eGFR <15 mL/min per 1&#xb7;73 m2, or initiation of kidney replacement therapy), kidney-related death, or cardiovascular-related death. Safety was also assessed. FINDINGS: The pooled participants from the trials (N=30&#x2008;787) had a mean follow-up of 39&#xb7;5-47&#xb7;5 months. Among participants assigned to semaglutide, 973 first events of the primary kidney composite occurred compared with 1134 first events for placebo (hazard ratio [HR] 0&#xb7;84 [95% CI 0&#xb7;77-0&#xb7;91]). First events of a narrower secondary kidney composite (excluding cardiovascular-related death from the primary outcome) were also reduced with semaglutide versus placebo (347 and 416, respectively; 0&#xb7;80 [0&#xb7;69-0&#xb7;92]). Safety outcomes were overall similar between groups, and in line with other GLP-1 receptor agonist trials. Serious adverse events were numberically lower with semaglutide than with placebo. INTERPRETATION: Data pooled from three large phase 3 trials suggest that semaglutide reduces the risk of major kidney outcomes in a broad population with cardio-kidney-metabolic disease while having a favourable risk-benefit profile. In people with cardio-kidney-metabolic disease, with and without diabetes, semaglutide (oral or injected) prevents kidney-related and cardiovascular complications and induces adverse events in line with GLP-1 receptor agonist studies, regardless of baseline characteristics within the cardio-kidney-metabolic spectrum. This was a participant-level analysis conducted in a large database of three randomised controlled trials of similar design and examining the same treatment, but there were some differences in participants' baseline characteristics, and in the dose and route of administration of treatment. This pooled analysis adds evidence for the benefit of GLP-1 receptor agonists in general, and semaglutide in particular, in a broad population of people with cardio-kidney-metabolic disease, suggesting that the benefit of semaglutide might not be explained only by its glycaemic effects, weight-management effects, or both. FUNDING: Novo Nordisk.

Humans↗
PubMed2026

A validated, modifiable proteomic score from the EXSCEL trial predicts cardiovascular events in diabetes.

BACKGROUNDAdults with type 2 diabetes mellitus (T2DM) are at increased risk for stroke, myocardial infarction, and cardiovascular death, yet individual risk is heterogeneous and incompletely captured by clinical models.METHODSIn the Exenatide Study of Cardiovascular Event Lowering (EXSCEL), adults with T2DM were randomized to a GLP-1 RA (exenatide) or a placebo and followed longitudinally for major adverse cardiovascular events (MACE). High-throughput discovery proteomics was done in plasma collected at baseline and 12 months. Proteins associated with time to MACE were identified using multivariable regression and incorporated into supervised machine learning models. A multi-protein score was developed and externally validated in 2 independent population-based and trial cohorts.RESULTSThe proteomic score showed incremental improvement in cardiovascular risk discrimination beyond clinical factors alone, and several proteins were consistently prioritized across modeling approaches. The protein score and a top-ranked protein, tetranectin, were modified by GLP-1 RA treatment, and a decrease in protein score was associated with improved outcomes, supporting modifiability of MACE risk.CONCLUSIONExternal validation confirmed generalizability across cohorts with and without diabetes. Together, these findings demonstrate that plasma proteomic signatures can enhance cardiovascular risk stratification and identify treatment-responsive biomarkers in T2DM, supporting their potential role in precision prevention strategiesFUNDINGThe EXSCEL study was funded by Amylin Pharmaceuticals. This research was supported by contracts HHSN268201200036C, HHSN268200800007C, HHSN268201800001C, N01HC55222, N01HC85079, N01HC85080, N01HC85081, N01HC85082, N01HC85083, N01HC85086, 75N92021D00006, and grants R01HL146145, U01HL080295, U01HL130114, R01HL172803, and R01HL144483 from the National Heart, Lung, and Blood Institute, with additional contribution from the National Institute of Neurological Disorders and Stroke. Additional support was provided by R01AG023629 from the National Institute on Aging.

Aged↗
PubMed2025

Cellular Adhesion Molecules and Adverse Outcomes in Chronic Heart Failure: Findings From the DAPA-HF Randomized Clinical Trial.

IMPORTANCE: Vascular cell adhesion molecule 1 (VCAM-1) and intracellular cell adhesion molecule 1 (ICAM-1) are responsible for immune cell-cell interactions. Systemic levels of VCAM-1 are associated with incident heart failure (HF). OBJECTIVES: To determine if VCAM-1 and ICAM-1 levels are associated with progression of established HF. DESIGN, SETTING, AND PARTICIPANTS: Participants enrolled in the biomarker substudy of the Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure (DAPA-HF) randomized clinical trial had VCAM-1 and ICAM-1 levels measured at baseline and 12 months. The DAPA-HF trial was conducted at 410 sites in 20 countries. Patients with HF and reduced ejection fraction (HFrEF) in New York Heart Association (NYHA) class II to IV with elevated natriuretic peptides were enrolled between February 15, 2017, and August 17, 2018, with final follow-up on June 6, 2019. Data were analyzed from January 2023 to January 2025. INTERVENTIONS: Dapagliflozin, 10 mg, once daily vs placebo. MAIN OUTCOMES AND MEASURES: The primary outcome was the composite of a worsening HF event or cardiovascular death. The associations between VCAM-1 and ICAM-1 levels at baseline and the primary outcome, its components, and all-cause death were analyzed using Cox proportional hazards regression models adjusted for known prognostic variables including estimated glomerular filtration rate (eGFR), N-terminal pro-B-type natriuretic peptide (NT-proBNP), and high-sensitivity troponin T (hs-TnT), as well as high-sensitivity C-reactive protein. RESULTS: A total of 3051 participants (mean [SD] age, 67.2 [10.5] years; 2386 male [78.2%]) were included in this study. Mean (SD) follow-up time was 17.6 (5.2) months. The median (IQR) baseline VCAM-1 level was 997 (816.7-1218.8) ng/mL. Compared with patients with lower concentrations of VCAM-1, those with higher concentrations of VCAM-1 were older (mean [SD] age T3 vs T1, 69.7&#x2009;[9.7] years vs 64.1&#x2009;[10.7] years; P&#x2009;<&#x2009;.001), in worse NYHA class (T3 vs T1, NYHA class III/IV 35.6% [362 of 1017] vs 26.5% [269 of 1017]; P&#x2009;<&#x2009;.001), and had higher NT-proBNP (median [IQR] T3 vs T1, 2018 [1126-3753] pg/mL vs 1118 [693-1830] pg/mL) and hs-TnT (median [IQR] T3 vs T1, 24.7 [17.1-37.5] ng/L vs 16.6 [11.6-24.9] ng/L) concentrations, and lower eGFR (mean [SD] T3 vs T1, 58.4 [17.6] mL/min/1.73 m2 vs 71.7 [18.0] mL/min/1.73 m2). Patients in tertile 3 of VCAM-1, compared with tertile 1, had the highest risk of each outcome (eg, adjusted hazard ratio [HR] for primary outcome 1.40; 95% CI, 1.11-1.77; P&#x2009;=&#x2009;.004). ICAM-1 level was not associated with an elevated risk of any outcome. The benefit of dapagliflozin vs placebo in reducing the risk of the primary outcome was consistent across VCAM-1 tertiles: HR, 0.76 (95% CI, 0.54-1.06), 0.82 (95% CI, 0.59-1.12), and 0.77 (95% CI, 0.61-0.98) for tertiles 1, 2 and 3, respectively (P for interaction&#x2009;=&#x2009;.93). There was no significant change in VCAM-1 level with dapagliflozin at 52 weeks. CONCLUSIONS AND RELEVANCE: Results of this substudy of the DAPA-HF randomized clinical trial demonstrate that higher VCAM-1 levels, possibly reflecting a distinct inflammatory/immune pathophysiological pathway in HFrEF, were associated with worse outcomes, even after adjustment for conventional prognostic variables. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03036124.

Aged↗
PubMed2025

Cardiac Troponins and Cardiovascular Disease Risk Prediction: An Individual-Participant-Data Meta-Analysis.

BACKGROUND: The extent to which high-sensitivity cardiac troponin can predict cardiovascular disease (CVD) is uncertain. OBJECTIVES: We aimed to quantify the potential advantage of adding information on cardiac troponins to conventional risk factors in the prevention of CVD. METHODS: We meta-analyzed individual-participant data from 15 cohorts, comprising 62,150 participants without prior CVD. We calculated HRs, measures of risk discrimination, and reclassification after adding cardiac troponin T (cTnT) or I (cTnI) to conventional risk factors. The primary outcome was first-onset CVD (ie, coronary heart disease or stroke). We then modeled the implications of initiating statin therapy using incidence rates from 2.1 million individuals from the United Kingdom. RESULTS: Among participants with cTnT or cTnI measurements, 8,133 and 3,749 incident CVD events occurred during a median follow-up of 11.8 and 9.8 years, respectively. HRs for CVD per 1-SD higher concentration were 1.31 (95%&#xa0;CI: 1.25-1.37) for cTnT and 1.26 (95%&#xa0;CI: 1.19-1.33) for cTnI. Addition of cTnT or cTnI to conventional risk factors was associated with C-index increases of 0.015 (95%&#xa0;CI: 0.012-0.018) and 0.012 (95%&#xa0;CI: 0.009-0.015) and continuous net reclassification improvements of 6% and 5% in cases and 22% and 17% in noncases. One additional CVD event would be prevented for every 408 and 473 individuals screened based on statin therapy in those whose CVD risk is reclassified from intermediate to high risk after cTnT or cTnI measurement, respectively. CONCLUSIONS: Measurement of cardiac troponin results in a modest improvement in the prediction of first-onset CVD that may translate into population health benefits if used at scale.

Humans↗
PubMed2024

Blood-based epigenome-wide analyses of chronic low-grade inflammation across diverse population cohorts.

Chronic inflammation is a hallmark of age-related disease states. The effectiveness of inflammatory proteins including C-reactive protein (CRP) in assessing long-term inflammation is hindered by their phasic nature. DNA methylation (DNAm) signatures of CRP may act as more reliable markers of chronic inflammation. We show that inter-individual differences in DNAm capture 50% of the variance in circulating CRP (N&#xa0;= 17,936, Generation Scotland). We develop a series of DNAm predictors of CRP using state-of-the-art algorithms. An elastic-net-regression-based predictor outperformed competing methods and explained 18% of phenotypic variance in the Lothian Birth Cohort of 1936 (LBC1936) cohort, doubling that of existing DNAm predictors. DNAm predictors performed comparably in four additional test cohorts (Avon Longitudinal Study of Parents and Children, Health for Life in Singapore, Southall and Brent Revisited, and LBC1921), including for individuals of diverse genetic ancestry and different age groups. The best-performing predictor surpassed assay-measured CRP and a genetic score in its associations with 26 health outcomes. Our findings forge new avenues for assessing chronic low-grade inflammation in diverse populations.

Humans↗
PubMed2006

Effects of aldosterone receptor blockade in patients with mild-moderate heart failure taking a beta-blocker.

AIMS: Spironolactone improves prognosis in severe heart failure (HF). We investigated its effects in patients with mild-moderate HF treated with an ACE inhibitor and beta-blocker. METHODS AND RESULTS: Randomised, double-blind, parallel-group, 3-month comparison of placebo and spironolactone (25 mg daily) in 40 patients in New York Heart Association (NYHA) class I (20%), II (70%) or III (10%), with a left ventricular ejection fraction of <40%. The mean (standard error) changes from baseline in the spironolactone and placebo groups were, respectively: i) B-type natriuretic peptide (BNP) -53.4(22.2) pg/mL and +3.3(12.1) pg/mL, P=0.04, ii) pro-collagen type III N-terminal amino peptide (PIIINP) -0.6(0.2) micromol/L and +0.02(0.2) micromol/L, P=0.02 and iii) creatinine +10.7(3.2) micromol/L and -0.3(2.6) micromol/L, P=0.01. Compared with placebo, spironolactone therapy was associated with a reduction in self-reported health-related quality of life: change in visual analog score: -6 (3) vs. +6 (4); P=0.01. No differences were observed on other biochemical, neurohumoral, exercise and autonomic function assessments. CONCLUSION: In patients with mild-moderate HF, spironolactone reduced neurohumoral activation (BNP) and a marker of collagen turnover (PIIINP) but impaired renal function and quality of life. The benefit-risk ratio of aldosterone blockade in mild HF is uncertain and requires clarification in a large randomised trial.

Adrenergic beta-Antagonists↗
PubMed2006

Effect of prior moderate exercise on postprandial metabolism in men with type 2 diabetes: heterogeneity of responses.

UNLABELLED: Prior moderate exercise has been shown consistently to reduce postprandial triglyceride (TG) concentrations in non-diabetic adults, but its effects in men with type 2 diabetes are not known. This study aimed to determine the effect of moderate exercise on postprandial metabolism in men with type 2 diabetes. Ten middle-aged men with type 2 diabetes underwent two oral fat tolerance tests (blood taken fasting and for 8 h after a meal containing 80 g fat, 70 g carbohydrate) in random order. On the afternoon before one test, participants performed a 90-min treadmill walk (Exercise); no exercise was performed before the CONTROL test. Exercise significantly reduced fasting glucose ( CONTROL: 9.08+/-0.75 mmol l(-1), Exercise: 8.40+/-0.72 mmol l(-1), p=0.033) and insulin ( CONTROL: 8.01+/-0.98 microU ml(-1), Exercise: 6.81+/-0.93 microU ml(-1), p=0.046) and increased fasting 3-hydroxybutyrate ( CONTROL: 87.1+/-19.2 micromol l(-1), Exercise: 134.3+/-28.4 micromol l(-1), p=0.011); reduced postprandial insulin by 11.0% (p=0.04) and increased postprandial 3-hydroxybutyrate by 31.8% (p=0.03); but did not significantly change fasting or postprandial triglyceride or NEFA concentrations. However, the exercise-induced change in postprandial triglyceride concentration ranged from -32.3 to +28.3% and the exercise-induced change in fasting 3-hydroxybutyrate concentration (a marker of hepatic fatty acid oxidation) was highly correlated with the exercise-induced changes in fasting and postprandial triglyceride (r=0.68, p=0.03 for both). Thus, inter-individual variation in propensity to increase hepatic fatty acid oxidation following exercise may account for the considerable heterogeneity in triglyceride responses to moderate exercise observed in men with type 2 diabetes.

Adult↗
PubMed2006

Benefits of salmon eating on traditional and novel vascular risk factors in young, non-obese healthy subjects.

AIM: The present clinical study tested the hypothesis that oil-rich fish consumption improves CHD risk factors. METHODS: Forty-eight (16 men) non-obese, healthy adults aged 20-55, consumed 125 g/day of salmon for a 4-week period followed by a 4-week period with no-fish (41 completers). Subjects were instructed to maintain dietary and physical activity patterns during the period of study. Blood pressure, anthropometric, body composition and dietary information with fasting blood samples to determine traditional and novel CHD risk markers and plasma fatty acids were obtained before and after each period. RESULTS: Compared to no-fish, eating salmon significantly decreased systolic, diastolic and mean arterial blood pressure by 4%, triglycerides by 15%, and LDL-cholesterol by 7%, and significantly increased HDL-cholesterol by 5% (P<0.05). The changes in blood pressure and lipids alone with salmon intake predict around a 25% reduction in CHD risk based on the PROCAM risk calculator. Plasma adiponectin demonstrated a trend towards improvement (8.39 micromol/L with salmon and 7.52 with no-fish; P=0.086) but no significant changes were found either in plasma leptin, glucose or insulin after salmon consumption. CONCLUSIONS: Daily consumption of salmon improves traditional risk predictors of CHD in non-obese subjects. Adiponectin may be involved but the impact on novel risk factors needs study in high-risk subjects.

Adult↗
PubMed2006

Effects of metformin on microvascular function and exercise tolerance in women with angina and normal coronary arteries: a randomized, double-blind, placebo-controlled study.

OBJECTIVES: This study sought to determine whether metformin improves vascular function or myocardial ischemia in nondiabetic subjects. BACKGROUND: Metformin prevents diabetes and may reduce coronary events in patients with diabetes, but effects on microvascular function and angina are not clear. METHODS: We conducted an 8-week double-blind, randomized, placebo-controlled study of metformin 500 mg twice a day in 33 nondiabetic women with a prior history of normal coronary angiography but two consecutive positive (ST-segment depression > or =1 mm) exercise tolerance tests. All parameters were measured at baseline and at 8 weeks, together with an in vivo assessment of forearm (skin) microvascular function using laser Doppler imaging combined with iontophoresis. RESULTS: In comparison with placebo (n = 17), metformin recipients (n = 16) showed significant reductions in weight and in homeostatic model assessment for insulin resistance (p < 0.05, intention to treat). Endothelium-dependent microvascular responses improved significantly with metformin (2-way repeated analysis of variance, p = 0.0003), but responses with placebo were unchanged (p = 0.50). A comparison of change in acetylcholine responses between metformin and placebo recipients was significant, whether analyzed by a 2-way analysis of variance (p < 0.0001) or change in area under curves (mean change +392 perfusion units, 95% confidence interval [CI] 20 to 764). Endothelium-independent responses were not altered. Maximal ST-segment depression (-0.84 mm, 95% CI -1.49 to -0.20, p = 0.013), Duke score (6.1 U, 95% CI 1.8 to 10.5, p = 0.008), and chest pain incidence (-0.11 episodes/day, 95% CI -0.22 to 0.00, p = 0.056) improved in metformin relative to placebo recipients. CONCLUSIONS: Metformin may improve vascular function and decrease myocardial ischemia in nondiabetic women with chest pain and angiographically normal coronary arteries. Larger controlled trials of longer duration are warranted.

Adult↗
PubMed2006

Adiponectin and coronary heart disease: a prospective study and meta-analysis.

BACKGROUND: There is uncertainty about the association between circulating concentrations of adiponectin and coronary heart disease (CHD) risk. We report new data from a prospective study in the context of a meta-analysis of previously published prospective studies. METHODS AND RESULTS: We measured baseline adiponectin levels in stored serum samples of 589 men with fatal CHD or nonfatal myocardial infarction and in 1231 controls nested within a prospective study of 5661 men (aged 40 to 59 years) recruited during 1978-1980, as well as in paired samples obtained 4 years apart from 221 of these participants. Baseline adiponectin concentrations correlated (P < 0.0001) positively with HDL cholesterol (r = 0.33) and inversely with C-reactive protein (r = -0.11) and BMI (r = -0.21), and the year-to-year consistency of adiponectin values was comparable to those of blood pressure and total cholesterol levels. No significant difference between median adiponectin levels at baseline was observed between cases and controls (10.2 versus 10.8 microg/mL; P = 0.5), despite the fact that body mass index, HDL, and C-reactive protein were all significant predictors of events in this cohort. The odds ratio for CHD was 0.89 (95% CI, 0.67 to 1.18) in a comparison of men in the top third of adiponectin concentrations compared with those in the bottom third, similar to a meta-analysis (including the present study) of 7 prospective studies involving a total of 1318 CHD cases (odds ratio, 0.84 [95% CI, 0.70 to 1.01]). CONCLUSIONS: In contrast to the strong associations previously reported between adiponectin levels and risk of type 2 diabetes, any association with CHD risk is comparatively moderate and requires further investigation.

Adiponectin↗